Immunologic Tolerance to a Hapten

Abstract

Abstract The induction of tolerance to the TNP hapten in populations of B cells in various states of differentiation was studied with the free, reactive hapten trinitrobenzene-sulfonic acid (TNBS). An adoptive transfer system was used in which tolerance was induced in an adoptively transferred B cell source before the addition of reconstituting thymus cells and immunization with hapten-carrier. Bone marrow cells and cells from fetal liver were rendered tolerant to TNP in this manner, showing that tolerance can be induced in cells from the primary B cell precursor and stem cell source of both the adult and fetal mouse. Tolerance was induced in normal spleen cells after adoptive transfer and in spleen cells from ATXBM mice (B cell spleens) after transfer to ATX hosts. These experiments show the induction of tolerance to TNP in B cells in another state of differentiation (peripheral B cells). Tolerance could be induced in B cell sources depleted of T cells indicating that immunologic tolerance to TNP may be induced in B cells in the absence of T cells. The possibility of residual TNBS affecting the thymus cells used for reconstitution was ruled out by transferring fetal liver cells to a secondary host after tolerance induction in a primary adoptive host, and also by rendering ATXBM mice tolerant before the transfer of their spleen cells to an adoptive host. These maneuvers remove the B cells from the environment used for tolerance induction, and indicate that TNBS did not act upon reconstituting thymus cells. The data indicate that tolerance to TNP can be induced in early differentiation states of the B cell.